KR890015990A - Carbonylating Arylalkyl Halides - Google Patents

Abstract

A method is provided for the preparation of alpha-arylpropionic acids such as ibuprofen by carbonylating the corresponding 1-arylethyl halide in an acidic aqueous medium containing a palladium catalyst. In the preparation of ibuprofen, 1-(4 min -isobutylphenyl)ethyl halide is reacted with carbon monoxide in an acidic aqueous medium containing a palladium catalyst.

Description

Carbonylating Arylalkyl Halides

Since this is an open matter, no full text was included.

Claims (36)

A method of producing alpha-aryl propionic acids, comprising carbonylating arylethyl halides with carbon monoxide in an acidic aqueous medium in the presence of a palladium catalyst. The method of claim 1, wherein the palladium catalyst is at least selected from the group consisting of trivalent phosphorus compounds, carbonyl compounds, pi (pi-)-alkyl groups, amines, oximes, and compounds containing olefins A method comprising a palladium compound complexed with one ligand. The method of claim 2, wherein the ligand is tri (organo) phosphine. 4. The method of claim 3, wherein said ligand is triphenyl phosphine. 5. The process of claim 4 wherein said catalyst is a palladium bis (triphenyl phosphine) dichloro complex. The method of claim 1 wherein said acidic aqueous medium comprises dissociated hydrogen and halogen ions. 7. The method of claim 6, wherein the source of hydrogen ions and halogen ions is hydrogen halide. 8. The method of claim 7, wherein said hydrogen halide is hydrogen chloride. 8. The method of claim 7, wherein said hydrogen halide is hydrogen bromide. 7. The method of claim 6, wherein the molar ratio of each of the dissociated hydrogen ions and halogen ions: the arylethyl halide is about 0.1-5. The method of claim 10, wherein the molar ratio of each of the dissociated hydrogen ions and halogen ions: the arylethyl halide is about 0.2-2.0. The method of claim 1 wherein the acidic aqueous medium comprises an organic solvent. The process of claim 1 wherein the carbonylation is performed at a temperature of about 10 to 225 ° C. and a CO pressure of about 100 to 5,000 psig. The method of claim 1 wherein said arylethyl halide is arylethyl chloride. The method of claim 1 wherein said arylethyl halide is arylethyl bromide. The compound of claim 1, wherein the arylethyl halide is 1- (3'-benzoylphenyl) ethyl chloride, 1- (2'-fluoro-4'-biphenylyl) ethyl chloride, 1- (2'-chloro -4'-biphenylyl) ethyl chloride, 1- (2'-fluorenyl) ethyl chloride, '1- (2'-xanthenyl) ethyl chloride, 1- (5H- [1] benzopyrano [ 2,3b] pyridin-7-yl) ethyl chloride, 1- (2'-biphenylenyl) ethyl chloride, 1- (6'-methoxy-2'-naphthyl) ethyl chloride, 1 (4'- Methoxyphenyl) ethyl chloride, or 1-phenyl ethyl chloride. The method of claim 1, wherein the alpha-arylpropionic acid is represented by the general formula: Wherein AR represents phenyl or multinuclear aromatic, which may be substituted with an unreactive group selected from alkyl, cycloalkyl, aryl, halogen, alkoxy, phenoxy, and ketone. The method of claim 1, wherein the alpha-arylpropionic acid is 2- (3'-benzoyl phenyl) propionic acid, 2- (2'-fluoro-4'-biphenylyl) propionic acid, 2- (2'-chloro-4 '-Biphenylyl) propionic acid, 2- (2'-fluoroenyl) propionic acid, 2- (2'-xanthenyl) propionic acid, 2- (5H- [1] benzopyrano [2,3b] pyridine -7-yl) propionic acid, 2- (2'-biphenylenyl) propionic acid, 2- (6'-methoxy-2-naphthyl) propionic acid, 2- (4'-methoxy phenyl) propionic acid, and 2 The process is phenyl propionic acid. A method for producing ibuprofen, comprising carbonylating 1- (4'-isobutylphenyl) ethyl halide with carbon monoxide in an acidic aqueous medium in the presence of a palladium catalyst. 20. The method according to claim 19, wherein the palladium catalyst is at least one ligand selected from the group consisting of trivalent phosphorus compounds, carbonyl compounds, py-allyl groups, amines, oximes, and compounds containing olefins. A method comprising a complexed palladium compound. The method of claim 20, wherein said ligand is tri (organo) phosphine. The method of claim 21, wherein said ligand is triphenylphosphine. 23. The process of claim 22, wherein said catalyst is a palladium bis (triphenyl phosphine) dichloro complex. 20. The method of claim 19, wherein said acidic aqueous medium comprises dissociated hydrogen and halogen ions. The method of claim 24, wherein the source of hydrogen ions and halogen ions is hydrogen halide. The method of claim 25, wherein said hydrogen halide is hydrogen chloride. The method of claim 25, wherein said hydrogen halide is hydrogen bromide. The method of claim 24, wherein the molar ratio of each of the dissociated hydrogen ions and halogen ions: the arylethyl halide is about 0.1-5. The method of claim 24, wherein each molar ratio of dissociated hydrogen ions and halogen ions: the arylethyl halide is about 0.2-2.0. 20. The method of claim 19, wherein the acidic aqueous medium comprises an organic solvent. 20. The method of claim 19 comprising carbonylating 1- (4'-isobutylphenyl) ethyl chloride. 20. The process of claim 19 comprising carbonylating 1- (4'-isobutylphenyl) ethyl bromide. Under reaction conditions sufficient to obtain 1- (4'-isobutylphenyl) ethyl halide, isobutylbenzene is reacted with a haloalkylating agent in the presence of Lewis acid, and in an acidic aqueous medium in the presence of a carbonylation catalyst A process for preparing ibuprofen from isobutylbenzene, comprising reacting 1- (4'-isobutylphenyl) ethyl halide with carbon monoxide to produce ibuprofen. 34. The process of claim 33, wherein the carbonylation catalyst is a palladium catalyst. 34. The method of claim 33, wherein the haloalkylating agent is acetaldehyde, paraaldehyde, 1,1-dimethoxyethane, di- (1-chloroethyl) ether with HCl, HBr, or HI. 36. The method of claim 35, wherein said haloalkylating agent is acetaldehyde with HCl. ※ Note: The disclosure is based on the initial application.